Fasting and stimulated glucagon-like peptide-1 exhibit a compensatory adaptive response in diabetes and pre-diabetes states: A multi-ethnic comparative study

Front Endocrinol (Lausanne). 2022 Sep 9:13:961432. doi: 10.3389/fendo.2022.961432. eCollection 2022.

Abstract

Background: Impaired secretion of glucagon-like peptide-1 (GLP-1) among Caucasians contributes to reduced incretin effect in type 2 diabetes mellitus (T2DM) patients. However, studies emanating from East Asia suggested preserved GLP-1 levels in pre-diabetes (pre-DM) and T2DM. We aimed to resolve these conflicting findings by investigating GLP-1 levels during oral glucose tolerance test (OGTT) among Malay, Chinese, and Indian ethnicities with normal glucose tolerance (NGT), pre-DM, and T2DM. The association between total GLP-1 levels, insulin resistance, and insulin sensitivity, and GLP-1 predictors were also analyzed.

Methods: A total of 174 subjects were divided into NGT (n=58), pre-DM (n=54), and T2DM (n=62). Plasma total GLP-1 concentrations were measured at 0, 30, and 120 min during a 75-g OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of insulin sensitivity (HOMA-IS), and triglyceride-glucose index (TyG) were calculated.

Results: Total GLP-1 levels at fasting and 30 min were significantly higher in T2DM compared with pre-DM and NGT (27.18 ± 11.56 pmol/L vs. 21.99 ± 10.16 pmol/L vs. 16.24 ± 7.79 pmol/L, p=0.001; and 50.22 ± 18.03 pmol/L vs. 41.05 ± 17.68 pmol/L vs. 31.44 ± 22.59 pmol/L, p<0.001; respectively). Ethnicity was a significant determinant of AUCGLP-1, with the Indians exhibiting higher GLP-1 responses than Chinese and Malays. Indians were the most insulin resistant, whereas Chinese were the most insulin sensitive. The GLP-1 levels were positively correlated with HOMA-IR and TyG but negatively correlated with HOMA-IS. This relationship was evident among Indians who exhibited augmented GLP-1 responses proportionately to their high insulin-resistant states.

Conclusion: This is the first study that showed GLP-1 responses are augmented as IR states increase. Fasting and post-OGTT GLP-1 levels are raised in T2DM and pre-DM compared to that in NGT. This raises a possibility of an adaptive compensatory response that has not been reported before. Among the three ethnic groups, the Indians has the highest IR and GLP-1 levels supporting the notion of an adaptive compensatory secretion of GLP-1.

Keywords: ethnicity; glucagon-like peptide-1; glucose tolerance; incretin; insulin resistance; pre-diabetes; secretion; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2*
  • Ethnicity
  • Fasting
  • Glucagon-Like Peptide 1
  • Humans
  • Incretins
  • Insulin
  • Insulin Resistance*
  • Prediabetic State*
  • Triglycerides

Substances

  • Blood Glucose
  • Incretins
  • Insulin
  • Triglycerides
  • Glucagon-Like Peptide 1